PD-1-Enhanced HIV-1 Therapeutic DNA Vaccine Shows Phase 1 Immunogenicity

Key Takeaways

• This first-in-human, randomized, double-blind, placebo-controlled, dose-escalation phase 1 trial evaluated ICVAX in adults with HIV-1 on ART at Shenzhen Third People’s Hospital.
• Treatment-related adverse events occurred in 83.3% of ICVAX recipients and 100% of placebo recipients, and all were mild, transient, and mainly local reactions.
• ELISpot responses were numerically higher than placebo across dose groups, and low-frequency Gag-specific T cells expressing CD107a and/or effector cytokines were observed among ICVAX recipients; the authors stated that efficacy will be assessed in future studies.

In a phase 1 evaluation of ICVAX, 75% of low-dose recipients and 75% of mid-dose recipients had at least a twofold peak ELISpot increase, versus 33.3% of pooled placebo recipients. ICVAX is a first-in-human PD-1-enhanced HIV-1 therapeutic DNA vaccine studied in adults with HIV-1 receiving ART at a single center in China.

NMPA approved this randomized, double-blind, placebo-controlled, dose-escalation phase 1 trial. It enrolled adults aged 18–50 years with HIV-1 who were already receiving antiretroviral therapy at enrollment. Participants entered sequential 1 mg, 2 mg, and 4 mg cohorts of 15, with 12 assigned to ICVAX and 3 to placebo in each cohort. They received intramuscular injections with electroporation at Weeks 0, 4, 8, 12, and 36. Primary safety, secondary immunological outcomes, and exploratory virological outcomes were recorded, and all 45 participants completed follow-up.

Treatment-related adverse events occurred in 100% of placebo recipients and 83.3% of ICVAX recipients. All were mild and transient, and most were local reactions at the injection site. No more severe treatment-related safety signal was outlined in the available phase 1 summary.

Alongside the lead comparison in the low- and mid-dose groups, the high-dose cohort showed a 58.3% rate of a ≥2-fold peak ELISpot increase over baseline. Placebo responses came from a pooled group of nine participants across cohorts. ICVAX recipients also showed low-frequency Gag-specific T cells expressing CD107a and/or effector cytokines after vaccination. Exploratory virological outcomes were recorded, although the abstract did not detail those results. These findings describe immunogenicity within a phase 1 dataset and did not establish efficacy.

The authors concluded that ICVAX was well tolerated and elicited robust antigen-specific T-cell responses in ART-suppressed people with HIV-1. That interpretation was limited to tolerability and immune readouts observed during this phase 1 evaluation. It did not extend to clinical efficacy or detailed virological control claims. The authors stated that efficacy will be assessed in future studies.